FDA Grants BDD to HLA-LOH CDx for Targeted Therapies in Solid Tumors

The FDA has granted breakthrough device designation to the HLA-LOH assay as a companion diagnostic test for use in patients with solid tumors, according to a press release from Tempus.¹

The assay utilizes a machine learning model that evaluate data generated with the xT CDx assay, a next-generation sequencing (NGS) device. The test and assay operate in conjunction to identify patients with solid tumors experiencing allele-specific loss of heterozygosity for specific HLA class I alleles who may benefit from specific targeted therapies.

“HLA-LOH provides a clear molecular distinction between cancer and non-cancer cells and is a potential biomarker for immune therapy resistance,” Kate Sasser, PhD, chief scientific officer at Tempus, said in the press release. “The HLA-LOH test is intended to measure this biomarker and better understand which patients may respond to new therapies. This breakthrough device designation from the FDA recognizes the novelty and potential clinical impact of our HLA-LOH test for this promising biomarker.”

The FDA previously approved the xT CDx assay for assessing microsatellite instability (MSI) status among patients with colorectal cancer (CRC) in May 2023.² In particular, the assay was indicated for use in detecting KRAS wild type mutations with absence of mutations in codons 12 or 13 in those who may benefit from therapy with cetuximab (Erbitux).³ The test was also indicated for detecting KRAS wild-type mutations with absence of mutations in exons 2, 3, or 4 and NRAS wild-type mutations with absence of mutations in exons 2, 3, or 4 in patients who may be eligible to receive panitumumab (Vectibix).

Investigators evaluated the xT CDx assay’s ability to detect specific KRAS and NRAS variants across 69 CRC samples. Of 31 CDx variants that investigators identified through orthogonal methods (OM), 31 were detectable with the xT CDx assay, resulting in a positive percentage agreement of 100.0% (95% CI, 88.8%-100.0%). Moreover, the assay detected 648 negative variants of a collective 649 that were identified via OM as being negative, yielding a negative percentage agreement of 99.8% (95% CI, 99.1%-100.0%).

“We designed xT CDx to be a smart test that can empower physicians to provide personalized care for their patients and support researchers in developing better therapeutics,” Eric Lefkofsky, founder and chief executive officer of Tempus, said in a press release at the time of the FDA’s approval of the assay.²

The xT CDx assay, an in vitro diagnostic device, is designed to detect single nucleotide variant and multi-nucleotide variant substitutions, determine MSI status, and identify insertion and deletion alterations in 648 genes. The assay uses DNA extracted from formalin-fixed paraffin embedded tumor tissue samples and matched normal blood or saliva samples from patients with solid malignant neoplasms.

According to the xT CDx assay’s technical information, it is intended for in vitro diagnostic use and for prescription use only.³ Additionally, the assay is not designed to assess germline variants, and a negative result does not negate the presence of a mutation that falls below its minimum tumor threshold of 20% for detecting variants.

References

1. FDA grants breakthrough device designation to Tempus’ HLA-LOH companion diagnostic test. News release. Tempus. August 15, 2023. Accessed August 17, 2023. https://shorturl.at/szMPX
2. Tempus receives U.S. FDA Approval for xT CDx, a NGS-based in vitro diagnostic device. News release. Tempus. May 1, 2023. Accessed August 17, 2023. https://bit.ly/3p124gA
3. cT CDx technical information. Tempus. February 2023. Accessed August 17, 2023. https://bit.ly/3VsYCr1